KNSTRN

Summary

KNSTRN (kinetochore localized astrin (SPAG5) binding protein, HGNC:30767) is a protein-coding gene on chromosome 15q15.1, encoding Small kinetochore-associated protein (Q9Y448). Essential component of the mitotic spindle required for faithful chromosome segregation and progression into anaphase.

Enables microtubule plus-end binding activity and protein homodimerization activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; mitotic sister chromatid segregation; and regulation of attachment of spindle microtubules to kinetochore. Located in several cellular components, including kinetochore; microtubule cytoskeleton; and ruffle. Implicated in actinic keratosis and skin squamous cell carcinoma.

Source: NCBI Gene 90417 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 85 total — 1 pathogenic
• Phenotypes (HPO): 77
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_033286

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30767
Approved symbol	KNSTRN
Name	kinetochore localized astrin (SPAG5) binding protein
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14502, SKAP, kinastrin, TRAF4AF1
Ensembl gene	ENSG00000128944
Ensembl biotype	protein_coding
OMIM	614718
Entrez	90417

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 nonsense_mediated_decay, 5 protein_coding, 5 retained_intron

ENST00000249776, ENST00000416151, ENST00000448395, ENST00000557920, ENST00000559083, ENST00000559304, ENST00000559591, ENST00000559604, ENST00000560220, ENST00000560321, ENST00000560673, ENST00000560981, ENST00000561169, ENST00000561196, ENST00000561367, ENST00000608100

RefSeq mRNA: 3 — MANE Select: NM_033286 NM_001142761, NM_001142762, NM_033286

CCDS: CCDS42021, CCDS45226, CCDS45227

Canonical transcript exons

ENST00000249776 — 9 exons

Exon	Start	End
ENSE00002551368	40393469	40394288
ENSE00003464984	40391493	40391554
ENSE00003543796	40387159	40387206
ENSE00003556903	40391949	40392023
ENSE00003582568	40382721	40383044
ENSE00003608793	40383228	40383322
ENSE00003663535	40389506	40389611
ENSE00003680096	40386362	40386494
ENSE00003790880	40389836	40389929

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 97.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.4622 / max 331.8308, expressed in 1794 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146102	24.1361	1791
146101	0.1568	40
146103	0.1013	31
146098	0.0526	3
146100	0.0094	3
146099	0.0060	3

Top tissues by expression

246 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.49	gold quality
right lobe of thyroid gland	UBERON:0001119	96.89	gold quality
sperm	CL:0000019	96.47	gold quality
left lobe of thyroid gland	UBERON:0001120	95.87	gold quality
oocyte	CL:0000023	95.25	gold quality
ganglionic eminence	UBERON:0004023	94.63	gold quality
embryo	UBERON:0000922	94.62	gold quality
right testis	UBERON:0004534	94.41	gold quality
left testis	UBERON:0004533	94.38	gold quality
thyroid gland	UBERON:0002046	94.23	gold quality
testis	UBERON:0000473	92.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.79	gold quality
tibialis anterior	UBERON:0001385	89.47	silver quality
secondary oocyte	CL:0000655	87.28	gold quality
stromal cell of endometrium	CL:0002255	87.12	gold quality
ileal mucosa	UBERON:0000331	86.20	gold quality
cortical plate	UBERON:0005343	85.60	gold quality
adult organism	UBERON:0007023	84.66	gold quality
adrenal tissue	UBERON:0018303	84.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.42	gold quality
smooth muscle tissue	UBERON:0001135	84.25	gold quality
granulocyte	CL:0000094	83.76	gold quality
monocyte	CL:0000576	83.76	gold quality
leukocyte	CL:0000738	83.64	gold quality
bone marrow cell	CL:0002092	83.62	gold quality
rectum	UBERON:0001052	83.41	gold quality
gastrocnemius	UBERON:0001388	83.24	gold quality
bone marrow	UBERON:0002371	83.11	gold quality
cerebellar hemisphere	UBERON:0002245	82.94	gold quality
muscle of leg	UBERON:0001383	82.93	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting KNSTRN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-325	99.58	66.55	358
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-4699-5P	98.99	67.50	1210
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-3190-5P	98.87	64.89	1345

Literature-anchored findings (GeneRIF, showing 17)

• This paper identifies role of gene product of FLJ14502, named SKAP in the paper, in mitosis. SKAP promotes metaphase-to-anaphase transition by mediating seperase activation after spindle assembly checkpoint is satisfied in mitosis. (PMID:19667759)
• SKAP cooperates with CENP-E to orchestrate dynamic kinetochore-microtubule interaction for faithful chromosome segregation. (PMID:22110139)
• SKAP constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division. (PMID:23035123)
• These findings suggest that SKAP promotes ultraviolet rays-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19. (PMID:24718257)
• Findings suggest a role for kinetochore protein KNSTRN mutagenesis in cutaneous squamous cell carcinomas (SCCs) development. (PMID:25194279)
• Mechanistically, the N-terminal of SKAP binds to EB1, and its C terminus binds to IQGAP1 in migrating cells. (PMID:26242911)
• study reports presence of KNSTRN mutations in basal cell carcinomas (BCC); mutant KNSTRN disrupts sister chromatid cohesion and promotes genomic instability in functional assays; KNSTRN mutations in BCC appear to occur late in disease progression and are preferentially found in advanced tumors (PMID:26348826)
• KNSTRN Mutation, a Cutaneous Squamous Carcinoma-Specific Mutation is associated with Solid Tumors and Leukemias. (PMID:26433880)
• Molecular requirements for the inter-subunit interaction and kinetochore recruitment of SKAP and Astrin have been reported. (PMID:27095104)
• GSK3beta-SKAP-Kif2b signaling axis constitutes a dynamic link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division. (PMID:27982129)
• Data show that aurora-B regulates end-on conversion in human cells and indicate a late role for SPAG5 protein (Astrin)-SKAP complex in the end-on conversion process. (PMID:28751710)
• The authors show that the Astrin-SKAP complex binds synergistically to microtubules with the Ndc80 complex to form an integrated interface. (PMID:28841134)
• Recurrent somatic mutation p.Ala40Glu in KNSTRN gene is associated with basal proliferating actinic keratosis in accordance with invasive squamous cell cardinomas. This supports the impact of basal proliferative pattern in terms of progression (PMID:30972880)
• KNSTRN promotes tumorigenesis and gemcitabine resistance by activating AKT in bladder cancer. (PMID:33452459)
• Src-mediated tyrosine phosphorylation of PRC1 and kinastrin/SKAP on the mitotic spindle. (PMID:33510346)
• SKAP interacts with Aurora B to guide end-on capture of spindle microtubules via phase separation. (PMID:34554241)
• Phosphorylation of small kinetochore-associated protein induced by GSK3beta promotes cell migration and invasion in esophageal cancer. (PMID:35201967)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	knstrn	ENSDARG00000074379
mus_musculus	Knstrn	ENSMUSG00000027331
rattus_norvegicus	Knstrn	ENSRNOG00000009334

Protein

Protein identifiers

Small kinetochore-associated protein — Q9Y448 (reviewed: Q9Y448)

Alternative names: Kinetochore-localized astrin-binding protein, Kinetochore-localized astrin/SPAG5-binding protein, TRAF4-associated factor 1

All UniProt accessions (9): Q9Y448, H0YKD4, H0YKF8, H0YLA7, H0YLH8, H0YM11, H0YN50, H0YNN6, V9GY01

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the mitotic spindle required for faithful chromosome segregation and progression into anaphase. Promotes the metaphase-to-anaphase transition and is required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture. The astrin (SPAG5)-kinastrin (SKAP) complex promotes stable microtubule-kinetochore attachments. Required for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis, possibly by forming a link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division. May be involved in UV-induced apoptosis via its interaction with PRPF19; however, these results need additional evidences.

Subunit / interactions. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with SPAG5. Directly binds to microtubules, although at relatively low affinity. Interacts with CENPE; this interaction greatly favors microtubule-binding. Interacts with DSN1/MIS13; leading to localization to kinetochores. Interacts with MAPRE1/EB1; leading to localization to the microtubule plus ends. Interacts with PRPF19. Interacts with DYNLL1. Interacts with MAP4.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore. Cytoplasm. Cytoskeleton. Spindle pole. Microtubule organizing center.

Tissue specificity. Widely expressed, including in skin.

Disease relevance. Roifman-Chitayat syndrome (ROCHIS) [MIM:613328] An autosomal recessive digenic disorder characterized by global developmental delay, variable neurologic features such as seizures and ataxia, optic atrophy, dysmorphic facial features, distal skeletal anomalies, and recurrent invasive infections due to combined immunodeficiency. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Caused by the simultaneous occurrence of homozygous mutations in PIK3CD and KNSTRN. Cutaneous squamous cell carcinomas (SCC): A malignancy of the skin. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Disease susceptibility is associated with variants affecting the gene represented in this entry. Variant Phe-24 appears specific for UV-associated malignancies.

Domain organisation. The coiled coil regions mediate binding to kinetochores.

Induction. Degraded at the end of mitosis. Down-regulated upon exposure to nitric oxide.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y448-1	1	yes
Q9Y448-2	2
Q9Y448-3	3

RefSeq proteins (3): NP_001136233, NP_001136234, NP_150628* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033373	SKAP	Family

UniProt features (14 total): sequence variant 4, sequence conflict 3, coiled-coil region 2, splice variant 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y448-F1	68.55	0.38

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 128

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 417 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_CHROMOSOME_LOCALIZATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOCC_RUFFLE, GOBP_RESPONSE_TO_EPIDERMAL_GROWTH_FACTOR, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, GOBP_ORGANELLE_FISSION, FISCHER_G2_M_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_REGULATION_OF_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE, GOBP_MITOTIC_CELL_CYCLE

GO Biological Process (8): mitotic sister chromatid segregation (GO:0000070), microtubule cytoskeleton organization (GO:0000226), spindle organization (GO:0007051), chromosome segregation (GO:0007059), cell migration (GO:0016477), cell division (GO:0051301), regulation of attachment of spindle microtubules to kinetochore (GO:0051988), cellular response to epidermal growth factor stimulus (GO:0071364)

GO Molecular Function (3): protein homodimerization activity (GO:0042803), microtubule plus-end binding (GO:0051010), protein binding (GO:0005515)

GO Cellular Component (14): kinetochore (GO:0000776), spindle pole (GO:0000922), ruffle (GO:0001726), nucleus (GO:0005634), microtubule organizing center (GO:0005815), plasma membrane (GO:0005886), centriolar satellite (GO:0034451), microtubule plus-end (GO:0035371), mitotic spindle (GO:0072686), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), microtubule (GO:0005874)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membraneless organelle	3
cell cycle process	2
spindle	2
microtubule cytoskeleton	2
sister chromatid segregation	1
mitotic nuclear division	1
mitotic cell cycle process	1
cytoskeleton organization	1
microtubule-based process	1
microtubule cytoskeleton organization	1
cell motility	1
cellular process	1
attachment of spindle microtubules to kinetochore	1
regulation of cell cycle process	1
response to epidermal growth factor	1
cellular response to growth factor stimulus	1
identical protein binding	1
protein dimerization activity	1
microtubule binding	1
binding	1
condensed chromosome, centromeric region	1
supramolecular complex	1
cell leading edge	1
plasma membrane bounded cell projection	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
centrosome	1
microtubule end	1
chromosomal region	1
intracellular anatomical structure	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KNSTRN	SPAG5	Q96R06	934
KNSTRN	CENPE	Q02224	808
KNSTRN	CHMP1B	Q7LBR1	749
KNSTRN	STAMBP	O95630	716
KNSTRN	VPS4A	Q9UN37	669
KNSTRN	SKAP1	Q86WV1	658
KNSTRN	SPAST	Q9UBP0	649
KNSTRN	CLASP1	Q7Z460	630
KNSTRN	RASSF5	Q8WWW0	619
KNSTRN	SPOUT1	Q5T280	589
KNSTRN	DYNLL1	P63167	585
KNSTRN	SSRP1	Q08945	582
KNSTRN	APBB1IP	Q7Z5R6	578
KNSTRN	NUF2	Q9BZD4	542
KNSTRN	NUMA1	Q14980	508

IntAct

108 interactions, top by confidence:

A	B	Type	Score
PRPF19	AQR	psi-mi:“MI:0914”(association)	0.790
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
MAPRE1	KNSTRN	psi-mi:“MI:0915”(physical association)	0.740
KIF22	KPNA4	psi-mi:“MI:0914”(association)	0.730
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
SGF29	KNSTRN	psi-mi:“MI:0915”(physical association)	0.670
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
WASHC3	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
MAPRE3	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
PPL	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
BEX2	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
ABI2	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
OIP5	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
IFT20	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
Mad2l1	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
HTT	KNSTRN	psi-mi:“MI:0915”(physical association)	0.560
MYCBP	AKAP8	psi-mi:“MI:0914”(association)	0.550
KXD1	HIP1	psi-mi:“MI:0914”(association)	0.530
DEUP1	HIP1	psi-mi:“MI:0914”(association)	0.530
COPS7B	ZZEF1	psi-mi:“MI:0914”(association)	0.530

BioGRID (144): KNSTRN (Affinity Capture-RNA), KNSTRN (Affinity Capture-RNA), KNSTRN (Affinity Capture-RNA), KNSTRN (Affinity Capture-RNA), KNSTRN (Two-hybrid), KNSTRN (Two-hybrid), KNSTRN (Affinity Capture-MS), KNSTRN (Affinity Capture-MS), KNSTRN (Affinity Capture-MS), KNSTRN (Affinity Capture-MS), KNSTRN (Affinity Capture-MS), KNSTRN (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), HSPA1A (Affinity Capture-MS)

ESM2 similar proteins: A0A0D9SF12, A2A8T7, A6H7E2, A6NF36, A6NFA0, A6NI87, E1C7U0, P03246, P03247, P0DO92, P14355, P14683, Q0VG49, Q1HVF6, Q32LN6, Q3KPU7, Q3KSS3, Q4V7D2, Q4ZG55, Q5DU28, Q5JX69, Q5JX71, Q5R7E2, Q5U4U4, Q642A3, Q6NRW0, Q6P1U0, Q6P4J6, Q6P9N1, Q6PEX7, Q6X4T0, Q7L3B6, Q7SYV9, Q7T346, Q80Y73, Q8BJS8, Q8CF25, Q8IWB6, Q8N6T0, Q8NCU1

Diamond homologs: Q6AXN6, Q9D9Z1, Q9Y448

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
AURKA	“down-regulates activity”	KNSTRN	phosphorylation
KNSTRN	“down-regulates activity”	KIF2B	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 98 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Intraflagellar transport	7	25.5×	3e-06
Loss of Nlp from mitotic centrosomes	5	14.4×	1e-03
Loss of proteins required for interphase microtubule organization from the centrosome	5	14.4×	1e-03
AURKA Activation by TPX2	5	13.8×	1e-03
Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal	6	12.7×	1e-03
Recruitment of mitotic centrosome proteins and complexes	5	12.4×	2e-03
Regulation of PLK1 Activity at G2/M Transition	5	11.5×	2e-03
Recruitment of NuMA to mitotic centrosomes	5	10.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
non-motile cilium assembly	7	24.2×	5e-06
cell division	14	7.7×	2e-06
protein transport	10	5.2×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — SKCM.

Clinical variants and AI predictions

ClinVar

85 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	57
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1064712	NM_033286.4(KNSTRN):c.629del (p.Leu210fs)	Pathogenic

SpliceAI

1306 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40382931:G:GT	donor_gain	1.0000
15:40384600:G:GT	donor_gain	1.0000
15:40387205:GG:G	donor_gain	1.0000
15:40387206:GG:G	donor_gain	1.0000
15:40389486:A:AG	acceptor_gain	1.0000
15:40389487:A:G	acceptor_gain	1.0000
15:40389609:CAGG:C	donor_loss	1.0000
15:40389611:GGT:G	donor_loss	1.0000
15:40389612:GTA:G	donor_loss	1.0000
15:40389613:T:G	donor_loss	1.0000
15:40389825:T:TA	acceptor_gain	1.0000
15:40389831:A:AG	acceptor_gain	1.0000
15:40389831:AATAG:A	acceptor_gain	1.0000
15:40389832:A:G	acceptor_gain	1.0000
15:40389833:TAGG:T	acceptor_loss	1.0000
15:40389834:A:AG	acceptor_gain	1.0000
15:40389834:A:C	acceptor_loss	1.0000
15:40389834:AG:A	acceptor_gain	1.0000
15:40389834:AGG:A	acceptor_gain	1.0000
15:40389835:G:GA	acceptor_loss	1.0000
15:40389835:G:GG	acceptor_gain	1.0000
15:40389835:GG:G	acceptor_gain	1.0000
15:40389835:GGG:G	acceptor_gain	1.0000
15:40389835:GGGA:G	acceptor_gain	1.0000
15:40389928:AGGTA:A	donor_loss	1.0000
15:40389929:GGTA:G	donor_loss	1.0000
15:40389930:G:GG	donor_gain	1.0000
15:40389930:GTAA:G	donor_loss	1.0000
15:40389931:T:A	donor_loss	1.0000
15:40391945:TTA:T	acceptor_loss	1.0000

AlphaMissense

2052 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40389852:T:C	L203P	0.987
15:40391985:T:C	F262L	0.982
15:40391987:T:A	F262L	0.982
15:40391987:T:G	F262L	0.982
15:40389843:T:C	L200P	0.979
15:40391997:G:C	A266P	0.978
15:40389586:T:C	L189S	0.974
15:40391977:T:C	L259P	0.972
15:40391998:C:A	A266D	0.967
15:40389598:T:C	L193S	0.965
15:40389881:T:C	F213L	0.952
15:40389883:T:A	F213L	0.952
15:40389883:T:G	F213L	0.952
15:40391986:T:C	F262S	0.951
15:40393566:T:C	L307P	0.948
15:40389570:G:C	A184P	0.945
15:40389873:T:C	L210P	0.945
15:40393584:T:C	L313P	0.942
15:40391965:T:C	L255S	0.934
15:40389565:T:C	L182S	0.933
15:40389870:T:C	L209P	0.932
15:40393485:T:C	L280P	0.931
15:40392007:A:C	Q269P	0.921
15:40392019:T:C	L273S	0.921
15:40389544:T:C	L175P	0.908
15:40393511:T:C	F289L	0.903
15:40393513:C:A	F289L	0.903
15:40393513:C:G	F289L	0.903
15:40391985:T:A	F262I	0.901
15:40389557:C:A	N179K	0.896

dbSNP variants (sampled 300 via entrez): RS1000111067 (15:40391259 A>G), RS1000323465 (15:40389379 G>A,T), RS1000682260 (15:40386537 A>G), RS1000716312 (15:40392907 G>A,C), RS1000746002 (15:40394031 C>G), RS1000782154 (15:40387036 G>A), RS1000786349 (15:40382153 A>C,T), RS1000815187 (15:40386758 T>C), RS1000859848 (15:40381994 C>A), RS1000903339 (15:40380844 A>G), RS1001452766 (15:40382125 G>A), RS1001588586 (15:40382392 A>G), RS1001669424 (15:40383862 AAT>A), RS1001704109 (15:40394414 A>T), RS1001817315 (15:40388125 C>T)

Disease associations

OMIM: gene MIM:614718 | disease phenotypes: MIM:613328

GenCC curated gene-disease

Mondo (1): combined immunodeficiency with faciooculoskeletal anomalies (MONDO:0013226)

Orphanet (1): Combined immunodeficiency with facio-oculo-skeletal anomalies (Orphanet:221139)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000086	Ectopic kidney
HP:0000122	Unilateral renal agenesis
HP:0000306	Abnormality of the chin
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000490	Deeply set eye
HP:0000609	Optic nerve hypoplasia
HP:0000648	Optic atrophy
HP:0000924	Abnormality of the skeletal system
HP:0000938	Osteopenia
HP:0000953	Hyperpigmentation of the skin
HP:0000998	Hypertrichosis
HP:0001249	Intellectual disability
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001319	Neonatal hypotonia
HP:0001369	Arthritis
HP:0001537	Umbilical hernia
HP:0001761	Pes cavus
HP:0001999	Abnormal facial shape
HP:0002007	Frontal bossing
HP:0002014	Diarrhea
HP:0002020	Gastroesophageal reflux

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002579_11	Heschl’s gyrus morphology	5.000000e-06
GCST005846_5	Heart rate response to recovery post exercise (10 sec)	1.000000e-12
GCST005847_7	Heart rate response to recovery post exercise (20 sec)	2.000000e-11
GCST005850_4	Heart rate response to recovery post exercise (30 sec)	8.000000e-09
GCST010725_23	Malaria	2.000000e-06
GCST010725_38	Malaria	3.000000e-06
GCST010725_80	Malaria	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009185	heart rate response to recovery post exercise

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567641	Roifman-Chitayat Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
daidzein	affects expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
daidzin	affects cotreatment, affects expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	increases expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
genistin	affects cotreatment, affects expression	1
diallyl trisulfide	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
glycitein	affects cotreatment, affects expression	1
2-palmitoylglycerol	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
glycitin	affects cotreatment, affects expression	1
palbociclib	decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B2ZW	Abcam HEK293T KNSTRN KO	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.